The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives.

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.

Bibliometric analysis of interspinous device in treatment of lumbar degenerative diseases.

In recent years, with the introduction of the concept of lumbar non-fusion, the interspinous device has emerged. The purpose of this study is to bibliometrically analyze the state, areas of interest, and emerging trends in the usage of interspinous devices for the treatment of lumbar degeneration disease, as well as related research fields. Between January 1, 2000 and June 14, 2023, a comprehensive collection of publications on the topic of interspinous devices in the treatment of lumbar degenerative disease (IDTLDD) was procured from the Web of Science. A bibliometric analysis and visualization were subsequently conducted, utilizing various tools including HisCite, VOSviewer, CiteSpace, and bibliometrix package. This process involved the gathering of data on the country, institution, author, journal, reference, and keywords. A comprehensive analysis of 401 publications sourced from 149 journals was conducted, with 1718 authors affiliated with 1188 institutes across 240 countries/regions. Notably, the United States emerged as the leading contributor with 134 published articles on interspinous devices in the treatment of lumbar degenerative disease (33.42%). The most productive institution was Capital Medical University, with (10, 2.49%) publications. The author with the highest publication output was Block, Jon E, with 10 publications. European Spine Journal demonstrated the highest level of productivity, with a publication of (n = 39, 9.73%). The term "X-Stop" was the most frequently utilized keyword, followed by "Lumbar spinal stenosis." The study identified various topics of current interest, such as "Invasive decompression" and "Coflex." The present study provides a comprehensive survey of research trends and developments in the application of interspinous device for the treatment of lumbar degenerative diseases, including relevant research findings and collaborative efforts among authors, institutions, and countries.

Biomechanical Analysis of a Newly Proposed Surgical Combination (MIS Screw-Rod System for Indirect Decompression+ Interspinous Fusion System for long Term Spinal Stability) in Treatment of Lumbar Degenerative Diseases.

OBJECTIVE: The aim of this study is to analyze the biomechanical stability of a newly proposed surgical combination (minimally invasive surgery of screw-rod system for indirect decompression + interspinous fusion system for long term spinal stability) in treatment of lumbar degenerative diseases. METHODS: The three-dimensional (3D) computed tomography (CT) image data of an adult healthy male volunteer were selected. An intact model of L4/5 was further established and validated by using Mimic and 3-matic, 3D slicer, abaqus, Python. Four surgical models were constructed. The biomechanical stability among these surgical modes was compared and analyzed using finite element analysis. RESULTS: The maximum von mises on fixation system in surgical models 2 and 3 exhibited comparable values. This finding suggested that the increase in interspinous fusion did not result in a significant elevation in maximum von mises on fixation system. Compared with the third surgical model, the fourth model, which received less average von mises experienced by the screw in contact with both cancellous and cortical bone. The findings indicated that the inclusion of facet joint fusion in surgical procedures might not be necessary to increase the average von Mises stress experienced by the screw in contact with both cancellous and cortical bone. CONCLUSIONS: The biomechanical stability of the newly proposed surgical combination (MIS screw-rod for indirect decompression + interspinous fusion for long term spinal stability technique) was not lower than that of the other surgical combination groups, and it might not be necessary to perform facet joint fusion during the surgery.

Smoking index and COPD duration as potential risk factors for development of osteoporosis in patients with non-small cell lung cancer - A retrospective case control study evaluated by CT Hounsfield unit.

Objective: To investigate the effect of smoking index (calculated as number of cigarettes per day × smoking years) and chronic obstructive pulmonary disease (COPD) duration on osteoporosis (OP)evaluated by opportunistic chest CT in patients with non-small cell lung cancer (NSCLC). Methods: A total of 101 patients diagnosed with NSCLC were included in our cohort study. Among them, 50 patients with a history of smoking and COPD were assigned to the experimental group, while 51 patients without a history of smoking and COPD were assigned to the control group. Hounsfield unit (HU) value was measured by conventional chest CT to investigate the bone mineral density; and the mean values of axial HU value in the upper, middle and lower parts of T4, T7, T10 and L1 vertebral bodies were measured as the study variables. Results: There were no significant differences in gender, age, body mass index, type of lung cancer, clinical stage of lung cancer and comorbidities between the two groups (P = 0.938，P = 0.158，P = 0.722,P = 0.596,P = 0.813,P = 0.655). The overall mean HU values of T4, T7, T10, L1 in the experimental group were 116.60 ± 30.67, 110.56 ± 30.03, 109.18 (96.85-122.95), 94.63 (85.20-104.12) and 106.86 ± 22.26, respectively, which were significantly lower than those in the control group (189.55 ± 34.57, 174.54 ± 35.30, 172.73 (156.33-199.50), 158.20 (141.60-179.40) and 177.50 ± 33.49) (P ＜0.05). And in the experimental group, smoking index and COPD duration were significantly and negatively correlated with HU values (r = -0.627, -0.542, P ＜0.05, respectively). Conclusion: Patients with NSCLC who have a history of smoking and COPD exhibit a notably lower HU value compared to the control groups. Additionally, it has been observed that the smoking index and duration of COPD may be influential factors affecting bone mineral density in NSCLC patients.

The Potential Roles of Ferroptosis in Pathophysiology and Treatment of Musculoskeletal Diseases-Opportunities, Challenges, and Perspectives.

Ferroptosis is different from other forms of cell death, such as apoptosis, autophagy, pyroptosis, and cuproptosis, mainly involving iron metabolism and lipid peroxidation. Ferroptosis plays an important role in various disease, such as malignant tumors, neuron-degenerative diseases, and cardiovascular diseases, and has become the focus of current research. Both iron overload and lipid peroxide accumulation contribute to the occurrence, development, and treatment of musculoskeletal diseases, such as osteoporosis, osteoarthritis, osteosarcoma, intervertebral disc degeneration, and spinal cord injury. For a better understanding of the potential roles ferroptosis may play in pathophysiology and treatment of common musculoskeletal disorders, this article briefly reviewed the relationship and possible mechanisms. Through an investigation of ferroptosis' role in musculoskeletal diseases' occurrence, development, and treatment, ferroptosis could offer new opportunities for clinical diagnosis and treatment.

The analysis of the pyroptosis-related genes and hub gene TP63 ceRNA axis in osteosarcoma.

Pyroptosis is a type of programmed cell death that is associated with tumor development, prognosis, and therapeutic response. The significance of pyroptosis-related genes (PRGs) in the tumor microenvironment (TME) remains unclear. We examined the expression patterns of PRGs in 141 OS samples from two different datasets and characterized the genetic and transcriptional changes in PRGs. Based on these PRGs, all OS samples could be classified into two clusters. We discovered that multilayer PRG changes were linked to clinicopathological traits, prognosis, and TME characteristics in two separate genetic subtypes. The PRG score was then developed for predicting overall survival, and its predictive efficacy in OS patients was tested. As a result, we developed a very precise nomogram to improve the PRG-predictive model in clinical application. Furthermore, a competing endogenous RNA (ceRNA) network was built to find a LAMTOR5-AS1/hsa-miR-23a-3p/TP63 regulatory axis. Through experimental verification, it was found that the pyroptosis gene TP63 plays an important role in the regulation of osteosarcoma pyroptosis. The possible functions of PRGs in the TME, clinicopathological characteristics, and prognosis were established in our investigation of PRGs in OS. These findings may aid in our understanding of PRGs in OS as well as provide a novel way for prognostic evaluation and the creation of more effective immunotherapy treatments.

Identification of ferroptosis-associated biomarkers for the potential diagnosis and treatment of postmenopausal osteoporosis.

Objective: Postmenopausal osteoporosis (PMOP) is one of the most commonly occurring conditions worldwide and is characterized by estrogen deficiency as well as persistent calcium loss with age. The aim of our study was to identify significant ferroptosis-associated biomarkers for PMOP. Methods and materials: We obtained our training dataset from the Gene Expression Omnibus (GEO) database using GSE56815 expression profiling data. Meanwhile, we extracted ferroptosis-associated genes for further analysis. Differentially expressed ferroptosis-associated genes (DEFAGs) between OP patients and normal controls were selected using the "limma" package. We established a ferroptosis-associated gene signature using training models, specifically, random forest (RF) and support vector machine (SVM) models. It was further validated in another dataset (GSE56814) which also showed a high AUC: 0.98, indicating high diagnostic value. Using consensus clustering, the OP patient subtypes were identified. A ferroptosis associated gene (FAG)-Scoring scheme was developed by PCA. The important candidate genes associated with OP were also compared between different ferrclusters and geneclusters. Results: There were significant DEFAGs acquired, of which five (HMOX1, HAMP, LPIN1, MAP3K5, FLT3) were selected for establishing a ferroptosis-associated gene signature. Analyzed from the ROC curve, our established RF model had a higher AUC value than the SVM model (RF model AUC:1.00). Considering these results, the established RF model was chosen to be the most appropriate training model. Later, based on the expression levels of the five DEFAGs, a clinical application nomogram was established. The OP patients were divided into two subtypes (ferrcluster A, B and genecluster A, B, respectively) according to the consensus clustering method based on DEFAGs and differentially expressed genes (DEGs). Ferrcluster B and genecluster B had higher ferroptosis score than ferrcluster A and genecluster A, respectively. The expression of COL1A1 gene was significantly higher in ferrcluster B and gencluster B compared with ferrcluster A and gencluster A, respectively, while there is no statistical difference in term of VDR gene, COL1A2 genes, and PTH gene expressions between ferrcluster A and B, together with gencluster A and B. Conclusions: On the basis of five explanatory variables (HMOX1, HAMP, LPIN1, MAP3K5 and FLT3), we developed a diagnostic ferroptosis-associated gene signature and identified two differently categorized OP subtypes that may potentially be applied for the early diagnosis and individualized treatment of PMOP. The ER gene, VDR gene, IL-6 gene, COL1A1 and COL1A2 genes, and PTH gene are important candidate gene of OP, however, more studies are still anticipated to further elucidate the relationship between these genes and ferroptosis in OP.

A Newly Established Cuproptosis-Associated Long Non-Coding RNA Signature for Predicting Prognosis and Indicating Immune Microenvironment Features in Soft Tissue Sarcoma.

Cuproptosis, a new type of programmed cell death, is involved in the development and progression of malignancies. The study of cuproptosis-associated long non-coding RNAs (lncRNAs) in soft tissue sarcomas (STSs) is however limited. There is also uncertainty regarding the prognostic accuracy of cuproptosis-associated lncRNAs in STSs and their relationship to the tumor immune microenvironment. The aim of this study was to determine the prognostic significance of cuprotosis-associated lncRNAs in STSs and their relationship to the tumor immune microenvironment. Transcriptomic and clinical data from patients with STSs were obtained through The Cancer Genome Atlas (TCGA). Overall, 259 patients were randomly allocated to a training group or a testing group. In the training group, a cuproptosis-associated lncRNA signature was constructed, and the signature was verified in the testing group. On the basis of risk scores and clinical features, we later developed a hybrid nomogram. We also performed functional and tumor immune microenvironment analysis based on the cuproptosis-associated lncRNA signature. A signature of 5 cuproptosis-associated lncRNAs was created. Based on this signature, we categorized STS patients into high-risk and low-risk groups. The study showed that patients at high risk had a worse prognosis than those at low risk. A nomogram was then constructed combining clinical characteristics with the risk scores, and it was shown to have credible predictive power. Functional enrichment and tumor immune microenvironmental analyses showed that high-risk STSs tend to be immunologically sensitive tumors. In our study, we found a cuproptosis-associated lncRNAs signature, which serves as an independent prognostic indicator. Cuproptosis-associated lncRNAs may play a role in the tumor immune microenvironment, which might be a therapeutic target for patients with STSs.

Volume-controlled ventilation versus pressure-controlled ventilation during spine surgery in the prone position: A meta-analysis.

Background: Many studies have investigated a comparison of the potency and safety of PCV versus VCV modes in spinal surgery in prone position. However, controversy about the maximal benefits of which ventilation modes remains. The main purpose of this meta-analysis was to investigate which one is the optimal ventilation for surgery patients undergoing spine surgery in prone position between the two ventilation modes as PCV and VCV. Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, the Cochrane Library, and Google Scholar for potentially eligible articles. The continuous outcomes were analyzed using the mean difference and the associated 95% confidence interval. Meta-analysis was performed using Review Manager 5.4 software. Results: Our meta-analysis included 8 RCTs involving a total of 454 patients between 2012 and 2020. The results demonstrated that IOB, Ppeak and CVP for VCV are significantly superior to PCV in spinal surgery in prone position. And PCV had higher Cdyn and PaO2/FiO2 than VCV. But there was no significant difference between PCV and VCV in terms of POB, Hb, HCT, HR and MAP. Conclusions: The PCV mode displayed a more satisfying effect than VCV mode. Compared to VCV mode in same preset of tidal volume, the patients with PCV mode in prone position demonstrated less IOB, lower Ppeak and CVP, and higher PaO2/FiO2 in spinal surgery. However, there is no obvious difference between PCV and VCV in terms of hemodynamics variables (HR and MAP).

Drug fever induced by antibiotics of ß-lactams in a patient after posterior cervical spine surgery-A case report and literature review.

Drug fever is a febrile reaction that emerges temporarily with the administration of a drug or a variety of drugs and disappears after cessation of the targeting agent. There are a few previous reports about drug fever, but they pertain mainly to patients accompanied by no surgical intervention. Based on the literature reviewed, drug fever in patients after posterior cervical spine surgery has never been mentioned before; therefore, we present a 56-year-old man diagnosed with drug fever after posterior cervical spine surgery for traumatic cervical myelopathy. Fortunately, his body temperature rapidly came down in 2 days after discontinuing the antibiotics. He was discharged after two more days of observation, and the patient recovered well without any further complaints. Early diagnosis of drug fever may greatly reduce inappropriate and potentially detrimental diagnostic and therapeutic interventions. For patients with persistent fever, if it happened days after surgery, particularly when it is without any infectious evidence, then it is necessarily important to consider a possible reason of drug-induced fever.

Self-standing zeolite foam monoliths with hierarchical micro-meso-macroporous structures.

The zeolite monoliths were synthesized by a facile polymer scaffold template assisted hydrothermal method. The selected foam-shaped template of a polyurethane (PU) foam monolith, was used to prepare the self-standing zeolite foam (ZF) monolithic materials. The obtained ZF products can preserve the same size, shape and macroporous network structure of the original PU foam scaffold template, although the zeolite nano-crystallites had been fully substituted for the PU template to form the new skeleton struts and walls. The as-synthesized ZF products demonstrated abundant hierarchical porosity (involving triple micro-, meso- and macropores). Meanwhile, compared with the conventional zeolite powders, the self-standing ZF monolithic materials exhibited greater total pore volume and nearly three times higher mesopore volume, suggesting wider applications as catalysts, catalyst supports and adsorbents in industry.